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Biomedical subjects

M V Singer

Publications and source records attributed to M V Singer.

At least 199 records · Page 11Linked to original sources

Latency of pancreatic enzyme response to intraduodenal stimulants.

In six dogs with pancreatic fistulas, secretin (500 ng . kg-1 . h-1) was given to provide a flow of pancreatic juice of about 1 drop/s. Amylase concentration was measured in each drop before and after rapid intraduodenal injection of L-tryptophan, sodium oleate, and NaCl or after rapid intraportal injection of cholecystokinin (CCK). Latency of response (time between injection and a sustained increase in amylase output greater than the mean + 3 SD of prestimulation output) was 0.30 min to tryptophan and 0.33 min to oleate. These were significantly (P less than 0.01) less than the latency to intraportal CCK (0.53 min). Atropine and truncal vagotomy increased the latency to tryptophan and oleate 10-fold but had no effect on the latency to intraportal CCK. We conclude that, since the latency of amylase response to intraduodenal stimulants was shorter than to intraportal CCK, the initial response is probably not due to release of hormones. The finding that atropine and vagotomy increased latency of response to intraduodenal stimulants indicates that a vagovagal cholinergic reflex mediates the early pancreatic enzyme response to intestinal stimulants.

Amylases↗

Dose-related inhibition of gastric secretion by intraduodenal trypsinogen in dogs.

It has been shown previously that trypsinogen and its activation peptide but not trypsin decreased gastric secretion. The purpose of this work was to study the dose-action relation between the intraduodenal infusion of trypsinogen and gastric secretion. Three dogs provided with gastric and duodenal Thomas fistulae were stimulated by continuous i.v. perfusion of porcine gastrin I-II (6 microgram kg-1 h-1). Pancreatic juice was diverted to the exterior and gastric secretion was collected. Upon reaching a gastric secretory plateau, porcine trypsinogen was infused intraduodenally at doses of 5, 10, 20, 40, 80 and 160 mg. Each test was continued for a further 60 min. Control was made with isotonic saline. There was a dose-related inhibition of the gastrin-stimulated gastric acid output. This inhibition reached a maximum of 50% with 40 mg of intraduodenal trypsinogen, showing no increase with higher doses.

Animals↗

Further studies on the effect of cholecystokinin and secretin on the content of cyclic AMP, cyclic GMP, protein and calcium in pure pancreatic juice of dogs.

The present work deals with the time course of pancreatic secretion of cyclic AMP, cyclic GMP, calcium and protein in response to cholecystokinin (CCK) and secretin (S). Three dogs with gastric and duodenal Thomas cannulae were given 1 Clinical Unit/kg/h of secretin for 150 min. CCK was added to the infusion after the first 75 min. Only one dose of CCK (0.75, 1.5, 3, 6, 16 24 Ivy dog U/kg/h) was given in any one experiment. Pancreatic juice was collected at one minute intervals for the first 15 min. at the beginning of the CCK infusion and at 15 min. intervals thereafter. CCK induced a biphasic pattern of pancreatic secretion: within 3 to 10 min. flow rate, protein, calcium, cyclic AMP and cyclic GMP output peaked in a dose dependent parallel manner. Then, the maximal flow remained constant while protein output reached a steady state; its value was fairly similar to that of the early peak for 0.75 to 6 U and for 16 and 24 U, the steady state value was lower than the first peak value. The pattern of calcium output was similar to that of protein output. The output of cyclic AMP and cyclic GMP increased until the end of the CCK infusion. When CCK (3 U/kg) was given as an intravenous bolus injection without any background of secretin, cyclic AMP, cyclic GMP and protein outputs peaked within 3 min. and then decreased. The results show that not only calcium and protein but also cyclic AMP and cyclic GMP secretion in the pancreatic juice depends on CCK. Key words: Dog, secretin, cholecystokinin, pancreatic juice: cyclic AMP, cyclic GMP, calcium, protein.

Animals↗

[The effect of atropine on the pancreas].

The literature relating to the effect of atropine on exocrine pancreatic secretion in man and animals is critically reviewed. In most species basal secretion of volume, bicarbonate, and enzyme secretion are reduced by atropine, thus indicating some neural control of basal pancreatic secretion. The literature is replete with conflicting findings on the effect of atropine on pancreatic response to exogenous hormones. In well controlled studies atropine had no effect on the action of cholecystokinin-pancreozymin (CCK) or caerulein on the pancreas. Atropine either moderately depressed or did not alter the volume and bicarbonate response to secretin but constantly reduced enzyme secretion. With respect to pancreatic response to a meal, and to intestinal instillation of aminoacids, fat or HCL, all studies agree that pancreatic secretion is depressed by atropine. The recent finding that atropine did not alter the response of a transplanted denervated pancreas to intestinal stimulants suggests that atropine acts on the pancreas by interrupting an enteropancreatic vago-vagal reflex and not by blocking the action of hormones on the pancreas or by interfering with cholinergic facilitation of gastrointestinal hormone release.

Anesthesia↗

Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin-pancreozymin.

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin-pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg-1 h-1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg-1 h-1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg-1 h-1 of CCK and later for 12 and 24 U kg-1 h-1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.

Animals↗

Effect of glucagon on canine exocrine pancreatic secretion stimulated by a test meal.

The effect of glucagon on exocrine pancreatic secretion stimulated by a test meal was studied in three dogs with a chronic gastric fistula and a modified Thomas duodenal fistula which allows easier collection of pure pancreatic juice after a meal. Glucagon was given by continuous intravenous infusion in doses of 5, 10, 15, or 30 microgram/kg per hour, before and during a test meal. At each dose level glucagon significantly reduced the water and electrolyte secretion of the pancreas. At 15 and 30 microgram/kg per hour glucagon inhibited protein output; this effect was absent at lower doses. These findings demonstrate a dose-dependent inhibition by glucagon of the pancreatic bicarbonate and protein response to a meal. Inhibition of bicarbonate output was more sensitive to glucagon than that of protein output.

Animals↗

Pancreatic dose-response curves to cholecystokinin determined by two techniques in dogs.

Dose-response (DR) curves for pancreatic flow rate, bicarbonate and protein output to cholecystokinin (CCK) were determined by two techniques in six conscious dogs with gastric and duodenal Thomas fistulas. With the continuous DR technique G.I.H. CCK was given by intravenous infusion in doses from 0.75 to 24 Ivy dog units (U) kg(-1) . h(-1), starting with the lowest dose and doubling the dose every 45 min. With the single DR technique only one dose of CCK was infused on each test day. All studies were done with a fixed background of secretin (1 CU kg(-1) . h(-1)). The protein output of the two consecutive 15-min collection periods during 15 to 45 min after starting each CCK dose was taken as the index of response. The dose-response curves for pancreatic flow rate and bicarbonate output did not differ with the two techniques. The maximal protein output was higher with the single DR than with the continuous DR technique. This study suggests that the appropriate method for studying maximal pancreatic protein output is the single DR technique.

Animals↗

[Effect of alcohol on the human and animal pancreas (author's transl)].

In Germany alcohol is responsible for 40--60 per cent of cases with chronic or chronic relapsing pancreatitis. The histologic lesions for a long time remain clinically asymptomatic. Their degree depends on the duration and the total amount of alcohol which is ingested. Promoters of alcoholic damage to the pancraes are a high intake of fat and protein and a genetic disposition. Acute application of alcohol leads to an inhibition of pancreatic secretion when the entrance of gastric acid into the duodenum is prevented. Otherwise a weak stimulation occurs with release of secretin. Chronic application of alcohol after a few months abolishes the initially seen inhibition and leads to an increase of enzyme secretion of the gland. The raised concentration of protein in the pancreatic juice is the cause of precipitation of protein plugs, and thus probably leads to the alterations which are typical for chronic pancreatitis.

Alcoholism↗

[Pancreatic dose-response curves to cholecystokinin in dogs (author's transl)].

Dose-response (DR) curves for pancreatic flow rate, bicarbonate and protein output to cholecystokinin (CCK) were determined by two techniques in 3 conscious dogs with gastric and duodenal Thomas fistulas. With the continuous DR technique the dose of CCK was doubled each 45 minutes and with the single DR technique, only one dose of CCK was infused on each test day. The dose-response curves for pancreatic flow rate and bicarbonate output did not differ with the two techniques. The maximal protein output was higher with the single DR than with the continuous DR technique.

Animals↗

Effect of pancreatic polypeptide-antiserum on bombesin-stimulated pancreatic exocrine secretion in dogs.

Bombesin is a potent stimulus of both pancreatic protein secretion and plasma pancreatic polypeptide (PP) release in dogs. Physiological plasma levels of PP have been shown to inhibit pancreatic exocrine secretion in dogs. We examined the question whether the concomitant release of PP exerts a suppressive action on the pancreatic exocrine response to bombesin in dogs by measuring pancreatic exocrine secretion with and without in vivo immunoneutralization of PP with a high affinity PP-antiserum. Bombesin was infused in a dose of 150 ng/kg.hr, resulting in a rise of plasma PP from 24 +/- 5 to 224 +/- 25 pM (p less than 0.01). Before this bombesin infusion, 7 ml of normal rabbit serum had been administered to the dogs (n = 8). At a later stage, the study was repeated after administration of 7 ml of PP-antiserum to the same animals. The bombesin induced increase in pancreatic exocrine secretion during administration of PP-antiserum (flow rate 24 +/- 10 ml/hr, protein output 1.35 +/- 0.43 g/hr, and bicarbonate output 3.25 +/- 1.42 mmol/hr) was not significantly different from that during control rabbit serum (flow rate 21 +/- 7 ml/hr, protein output 1.26 +/- 0.38 g/hr, and bicarbonate output 3.18 +/- 1.10 mmol/hr). It is therefore concluded that the pancreatic exocrine response to bombesin is not affected by the concomitant secretion of PP.

Animals↗

Presence of plasma endotoxin is correlated with tumour necrosis factor receptor levels and disease activity in alcoholic cirrhosis.

Cytokines and plasma endotoxin were measured in a consecutive series of patients with alcoholic cirrhosis (AC). Endotoxaemia was found to be strongly correlated to increased plasma levels of functionally active tumour necrosis factor (TNF) receptors -p55 and -p75, TNF-alpha and the Child-Pugh stage of the disease. Our data support the hypothesis of the pathogenic role of lipopolysaccharide in hepatocellular damage of patients with AC.

Case-Control Studies↗

Action of ethanol and some alcoholic beverages on gastric acid secretion in anaesthetized rats.

The action of intragastric ethanol in various concentrations equivalent to those found in alcoholic beverages (1.5-40 v/v), ethanol 96% (v/v) and of some commonly ingested alcoholic beverages produced by alcoholic fermentation (beer, wine, champagne, martini and sherry) or by fermentation plus distillation (e.g. whisky, cognac, calvados, armagnac and rum) on gastric acid output (GAO) was studied in anaesthetized Wistar rats. Ethanol concentrations of 1.5%, 4% and 10% v/v did not significantly alter basal GAO, whereas all higher concentrations of ethanol (20%, 40% and 96% v/v) significantly (P < 0.05) and dose-dependently decreased the GAO. All alcoholic beverages produced by fermentation significantly increased GAO by 30-35% of maximal acid output (MAO; 48 micrograms/kg pentagastrin intramuscularly), whereas alcoholic beverages produced by fermentation plus distillation significantly decreased GAO as compared to control (isotonic glucose and distilled water). Glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of GAO as beer. Lyophilized fermented glucose at different concentrations (dilution of 1:20 to 1:1) dose-dependently stimulated GAO: the highest dilution (1:20) had no effect, the 1:5 dilution significantly increased gastric acid secretion similarly to that of beer and fermented glucose. The highest concentration of lyophilized fermented glucose (1:1) was as potent as the MAO after pentagastrin (90% of MAO). In conclusion, the present investigation shows for the first time that, in rats: (1) ethanol in a concentration > 10% v/v inhibits GAO; (2) lower ethanol concentrations (< 10% v/v) do not alter GAO; (3) alcoholic beverages produced by fermentation but not those produced by alcoholic fermentation plus distillation are powerful stimulants of GAO; (4) the stimulatory non-alcoholic ingredients of these alcoholic beverages are most likely produced during the process of fermentation of carbohydrates and removed during the following process of distillation.

Alcoholic Beverages↗

Regulation of Staphylococcus aureus-mediated activation of interleukin-18 in peripheral blood mononuclear cells.

Bacteria and bacterial antigens strongly induce cytokine secretion by peripheral blood leukocytes and thereby initiate an inflammatory cascade with potentially deleterious consequences for the host. The present study focussed on receptors and signal transduction pathways involved in activation of interleukin (IL)-18 by heat-inactivated Gram-positive Staphylococcus aureus Cowan strain I (SAC). Similarly to IL-12/IL-12p40, IL-10 and IFN-gamma, SAC dose-dependently activated IL-18. Secretion of IL-18 was independent of functional activity of IL-10, IL-12 or IFN-gamma. Lipoteichoic acid (LTA), a structural component of SAC, was not sufficient for activation of IL-18, while it dose-dependently induced IL-10. In contrast to IL-12, blockade of CD14 only partially diminished secretion of IL-18 and did not affect secretion of IL-10, suggesting involvement of other receptors (e.g., Toll-like receptors) in SAC responses. Further down-stream however, secretion of IL-10, IL-12 and IL-18 was uniformly inhibited by blockade of G-protein-mediated kinase activation by mastoparan. Secretion of IL-18 required phosphatidylinositol-3'-kinase, and secretion of IL-12 phosphotyrosine kinase activity. The data demonstrate that SAC potently activates secretion of IL-18 by peripheral blood mononuclear cells with differential involvement of cell-surface receptors and signal transduction pathways as compared to other natural killer- and T cell-promoting cytokines.

Dactinomycin↗

Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis--results of a field study.

BACKGROUND/AIMS: In the treatment of ulcerative colitis, 5-aminosalicylic acid is the standard therapy for both acute exacerbations of the disease and the maintenance of remission. Clinical studies have shown that olsalazine (Dipentum)--a prodrug converted to two molecules of 5-ASA by colonic bacteria-induces and maintains remission. This study aimed to investigate the efficacy and tolerability of olsalazine in patients with ulcerative colitis who were being treated in daily practice by private physicians specializing in gastroenterology. METHODOLOGY: A total of 260 patients with ulcerative colitis (aged 17-77 years, 116 men) were studied. The doses of olsalazine and the clinical data (including acute disease symptoms and the occurrence of adverse events) were recorded over a 6-month period. RESULTS: Twenty per cent of patients had pancolitis, 48% had left-sided disease and 32% had proctitis or proctosigmoiditis. At study entry, 86% of patients had active disease; the percentages of these patients in remission after 6 weeks and 6 months were 42% and 91%, respectively. Patients with active disease received a mean dose of olsalazine - 2324mg per day initially and 1325mg per day at 6 months. The corresponding figures for patients in remission at study entry were 1386mg and 1162mg per day, respectively. Seventy-three per cent of patients took olsalazine with food, as recommended. The overall rate of adverse events was low; no serious adverse events occurred. CONCLUSIONS: Olsalazine therapy resulted in a rapid regression in the acute symptoms of ulcerative colitis. Olsalazine was also effective in maintaining remission. The drug was well tolerated.

Adult↗